Clinical evidence suggest that there is a form of sensorineural deafness that is immunologically mediated and potentially treatable if recognized early. Progress in this field has been hampered by the inaccessibility of the human inner ear and the lack of a specific diagnostic test for autoimmune deafness. Experimental studies have shown that the defense mechanisms of the inner ear involve immunological responsiveness to antigens and/or pathogens and that the endolymphatic sac is an important part of the afferent limb of inner ear immunity. Furthermore, animal models have shown that these responses can serve either to protect the inner ear, or under other conditions lead to its dysfunction. Damage may occur through inappropriate activity directed toward inner ear tissue antigens or as the result of bystander injury resulting from the inflammatory process itself. The proposed research will define the basic mechanisms underlying inner ear immunity by characterizing the lymphocyte subpopulations and the regulatory lymphokines involved in these responses, and determine the source of lymphocytes that accumulate locally. The magnitude and permanence of the immune-mediated hearing loss will be addressed, as well as whether drug intervention can alter the outcome. Since we have histological evidence that immune-mediated hearing loss is associated with vascular occlusion, experiments are designed to examine cochlear blood flow during inner ear immune responses. Documentation of this mechanism of injury would form the basis of new therapeutic modalities for treating such disorders. Development of an animal model of autoimmune sensorineural hearing loss (ASNHL) is the focus of ongoing research. Hearing loss in these animals is associated with an antibody directed against inner ear tissue that we have also been able to identify in the sera of patients with suspected ASNHL. This proposal will examine the nature of this antigen and whether patients and the experimental animals share autoantibody reactivity to common antigenic epitopes as determined by 2-dimensional gel electrophoresis. This finding would be an important step in developing a diagnostic test for ASNHL in humans.